Elevated Piezo levels cause structural and functional alterations in Drosophila garland nephrocytes

Podocytes, epithelial cells of the glomerular filtration barrier, are constantly exposed to biomechanical forces. These include hydrostatic pressure and shear stress, which increase during diseases such as hypertension or diabetes. To sense and respond to such changes in their physical environment, podocytes express mechanosensors and mechanotransducers. To deepen our knowledge about renal mechanotransduction mechanisms, we used Drosophila nephrocytes. Nephrocytes and mammalian podocytes are highly similar in morphology and molecular make-up of the filtration barrier; thus, nephrocytes are considered the homologue cells to podocytes. In addition, nephrocytes also experience biomechanical forces because of haemolymph movement. Here, we investigated the role of the mechanotransducer Piezo in larval garland nephrocytes. Depletion of Piezo produces only a mild functional phenotype, whereas elevated Piezo levels result in a severe phenotype with functional and morphological disturbances. Increased Piezo levels also cause the accumulation of actin stress fibres, increased Cubilin expression, more acidic vesicles, increased mitochondrial mass and/or activity, and elevated superoxide levels.